A new research program in the field of molecular recognition is proposed. We plan to design, synthesize and study two classes of molecular receptors which will recognize and selectively bind important biological molecules. The first class of receptors will be specific for the phenethylamines which have many important functions in biochemistry (e.g. dopamine, phenylalanine, tyrosine and L-DOPA). Component binding site units (e.g. for ammonium, phenyl, carboxylate and phenolic OH groups) will be prepared and put together in various combinations to form the receptors. The first target will be a ditopic receptor, containing ammonium and phenyl group binding sites, which recognizes the basic phenethylamine nucleus. Detailed structural, thermodynamic and kinetic studies will be performed on this and later systems to probe the relationship between receptor and substrate structure and the complexation process. Different tri-tetra- and pentatopic receptors will be prepared to recognize different derivatives of phenethylamine. In addition receptors containing chiral and/or reactive groups will be synthesized. These receptors should find important application in the transport of drugs, new chromatographic materials and biosensors. The second class of receptors will recognize terminal peptide carboxylate species and will be based on the important vancomycin family of antibiotics. We will prepare synthetic analogs of the right hand ring of vancomycin. This region contains a hydrophobic pocket and key groups that hydrogen bond to the carboxylate terminus of AcD-Ala-D-Ala in bacterial cell wall biosynthesis. Preliminary results and calculations suggest that an isolated ring should have the same conformation and chemical characteristics as the natural system. The first target will be the basic right hand ring structure. To this we will sequentially add an in N-terminal residue and carboxamide group to increase the number of H-bonds to the substrate and thus the recognition characteristics of the receptor. In later targets we will accurately model substituents in the antibiotics. For each system we will use a variety of physical techniques (NMR, uv-vis, etc.) to probe the structure and selectivity of complexation. We will also collaborate to screen these receptors for antimicrobial activity.